Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin

Nature. 1993 Apr 29;362(6423):855-7. doi: 10.1038/362855a0.


During light-adaptation by the vertebrate eye, the rods are desensitized and the light response is accelerated. When light is absorbed by the rods, a phosphodiesterase is activated that hydrolyses cyclic GMP. A light-induced decrease in cytoplasmic Ca2+ concentration is part of this light-adaptation process. The protein S-modulin (M(r) 26,000) is known to increase the fraction of light-activated cyclic GMP-phosphodiesterase (PDE) at high Ca2+ concentrations in frog rod photoreceptors. Here I present evidence that S-modulin lengthens the lifetime of active PDE (PDE*) at high Ca2+ concentrations. These S-modulin effects are observed in the physiological range of Ca2+ concentration (30 nM to 1 microM; half-maximum effects at 200-400 nM). At the high Ca2+ concentrations at which S-modulin prolongs the lifetime of PDE*, S-modulin inhibits rhodopsin phosphorylation (half-maximum effect at approximately 100 nM Ca2+). ATP is necessary for the S-modulin effects on PDE activation. I therefore conclude that the Ca(2+)-dependent regulation of PDE by S-modulin is mediated by rhodopsin phosphorylation. This regulation seems to be the principal mechanism of light adaptation in vertebrate photoreceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Antigens, Neoplasm / metabolism*
  • Calcium / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Eye Proteins*
  • Hippocalcin
  • In Vitro Techniques
  • Light
  • Lipoproteins*
  • Nerve Tissue Proteins*
  • Phosphorylation
  • Rana catesbeiana
  • Recoverin
  • Rhodopsin / metabolism*
  • Rod Cell Outer Segment / metabolism


  • Antigens, Neoplasm
  • Calcium-Binding Proteins
  • Eye Proteins
  • Lipoproteins
  • Nerve Tissue Proteins
  • Recoverin
  • Hippocalcin
  • Adenosine Triphosphate
  • Rhodopsin
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Calcium